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LncRNA Malat1 suppresses pyroptosis and T cell-mediated killing of incipient metastatic cells [RNA-seq_4T1]

ABSTRACT: Malat1 was KO using paired gRNA CRISPR-cas9 system from 4T1 cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE183562 | GEO | 2023/09/18

REPOSITORIES: GEO

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LncRNA Malat1 suppresses pyroptosis and T cell-mediated killing of incipient metastatic cells [RNA-seq_4T1]

Project description:LncRNA Malat1 suppresses pyroptosis and T cell-mediated killing of incipient metastatic cells [RNA-seq_4T1]

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Identification of Malat1-chromatin interaction by ChIRP-seq

Project description:We performed Malat1 pulldown using biotin labeled Stellaris Oligo in 4T1-TGL WT cells.

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Differentiation of Mammary Tumors and Reduction in Metastasis Upon Malat1 LncRNA Loss

Project description:Genome-wide analyses have identified thousands of long non-coding RNAs (lncRNAs). Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genomic loss, as well as systemic knockdown of Malat1 using antisense oligonucleotides, in the MMTV-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by differentiation into highly cystic tumors and a significant reduction in lung metastasis. Further, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT and Her2/neu amplified tumor organoids consistent with the in vivo reduction in lung metastasis. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and pro-tumorigenic signaling pathways. Together, these data indicate that the lncRNA Malat1 regulates critical processes in mammary cancer pathogenesis and represents a promising therapeutic target for inhibiting breast cancer metastasis. Transcriptome profiles of tumors and organoids after Malat1 knockdown using antisense olgonucleotides (ASOs).

2016-01-12 | E-GEOD-67647 | biostudies-arrayexpress

lncRNA MALAT1 interactome - Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation

Project description:Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that was first discovered as a prognostic marker for lung cancer metastasis. MALAT1 has been implicated in the tumorigenesis of numerous tumor types. To further delineate the underlying molecular mechanism, we established a high-throughput strategy to characterize the interacting proteins of MALAT1 by combining RNA pull down, quantitative proteomics, bioinformatics analysis, and experimental validation.

2018-10-26 | PXD005154 | Pride

Alternative splicing modulation mediated by G-quadruplex structures in MALAT1 lncRNA

Project description:MALAT1, an abundant lncRNA specifically localized to nuclear speckles, regulates alternative-splicing (AS). The molecular basis of its role in AS remains poorly understood. Here, we report three conserved, thermodynamically stable, parallel RNA-G-quadruplexes (rG4s) present in the 3’ region of MALAT1 which regulates this function. Using rG4 domain specific RNA-pull-down followed by mass-spectrometry, RNA-immuno-precipitation and imaging, we demonstrate the rG4 dependent localization of Nucleolin (NCL) and Nucleophosmin (NPM) to nuclear speckles. Specific G-to-A mutations that abolish rG4 structures, results in the localization loss of both the proteins from speckles. Functionally, disruption of rG4 in MALAT1 phenocopies NCL knockdown resulting in altered pre-mRNA splicing of endogenous genes. These results reveal a central role of rG4s within the 3’ region of MALAT1 orchestrating AS.

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LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity

Project description:In this study, we performed RNA-seq to seek lncRNAs which changed significantly on expression in RAW264.7 cells before and after vesicular stomatitis virus (VSV) infection. For further investigation, we used iCLIP-seq technologies to identify the exact interaction sites between TDP43 protein and long non-coding RNA malat1 in mouse macrophages.

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Differential Gene expression in the mouse mammary tumors of PyMT-Malat1 wild-type (WT), PyMT-Malat1 knockout (KO) and PyMT-Malat1 knockout with Malat1 transgene expression (TG)

Project description:Previously, lncRNA Malat1 knockout mice were generated by insertional inactivation. By crossing this line to MMTV-PyMT mammary tumor mouse model, we produced PyMT;Malat1 wild-type (WT) and PyMT;Malat1 knockout (KO). Furthermore, we generated Malat1 transgenic mice by targeting ROSA26 locus and bred them to PyMT;Malat1 knockout mice to produce Malat1-rescued PyMT;Malat1 knockout;Malat1 transgenic animals (TG). Using mammary tumors from the three groups of animals, we performed RNA-Seq analysis to identify differentially up-regulated genes in KO tumors to find novel target genes of YAP-TEAD pathway.

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Project description:Microarrays were used to characterize the global changes in miRNA expression in EC109 cells due to siRNA knockdown of long non-coding RNA MALAT1

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Effect of lncRNA MALAT1 knockdown on gene expression of EC109 cells

Project description:microarrays were used to characterize the global changes in gene expression in EC109 cells due to siRNA knockdown of long non-coding RNA MALAT1

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